Lau, H. E. | bioRxiv Science

bioRxiv2021

SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters

Extrapulmonary complications of different organ systems have been increasingly recognized in patients with severe or chronic Coronavirus Disease 2019 (COVID-19). However, limited information on the skeletal complications of COVID-19 is known, even though inflammatory diseases of the respiratory tract have been known to perturb bone metabolism and cause pathological bone loss. In this study, we characterized the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bone metabolism in an established golden Syrian hamster model for COVID-19. SARS-CoV-2 causes significant multifocal loss of bone trabeculae in the long bones and lumbar vertebrae of all infected hamsters. The bone loss progressively worsens from the acute phase to the post-recovery phase. Mechanistically, the bone loss was associated with SARS-CoV-2-induced cytokine dysregulation which upregulates osteoclastic differentiation of monocyte-macrophage lineage. The pro-inflammatory cytokines further trigger a second wave of cytokine storm in the skeletal tissues to augment their pro-osteoclastogenesis effect. Our findings in this established hamster model suggest that pathological bone loss may be a neglected complication which warrants more extensive investigations during the long-term follow-up of COVID-19 patients. The benefits of potential prophylactic and therapeutic interventions against pathological bone loss should be further evaluated. O_FIG O_LINKSMALLFIG WIDTH=188 HEIGHT=200 SRC="FIGDIR/small/463665v1_ufig1.gif" ALT="Figure 1"> View larger version (81K): org.highwire.dtl.DTLVardef@ada9b8org.highwire.dtl.DTLVardef@1617fcaorg.highwire.dtl.DTLVardef@cdcd3org.highwire.dtl.DTLVardef@75a0ab_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical abstractSARS-CoV-2 infection causes pathological bone loss in golden Syrian hamsters through induction of cytokine storm and inflammation-induced osteoclastogenesis.

microbiology↗

bioRxiv2017

Neural mechanisms driving hunger-induced changes in sensory perception and behavior in Caenorhabditis elegans

Animals integrate changes in external and internal environments to generate behavior. While neural circuits detecting external cues have been mapped, less is known about how internal states like hunger are integrated into behavioral outputs. We use the nematode C. elegans to decode how changes in internal nutritional status affects chemosensory behaviors. We show that acute food deprivation leads to a reversible decline in repellent, but not attractant, sensitivity. This behavioral change requires two conserved transcription factors MML-1 (Mondo A) and HLH-30 (TFEB), both of which translocate from the intestinal nuclei to the cytoplasm upon food deprivation. Next, we identify insulin-like peptides INS-23 and INS-31 as candidate ligands relaying food-status signals from the intestine to other tissues. Furthermore, we show that ASI chemosensory neurons use the DAF-2 insulin receptor, PI-3 Kinase, and the mTOR complex to integrate these intestine-released peptides. Together, our study shows how internal food status signals are integrated by transcription factors and intestine-neuron signaling to generate flexible behaviors. Author SummaryWe have all experienced behavioral changes when we are hungry - the pang in our stomach can cause us to behave erratically. In particular, hungry animals, including humans, are known to pursue behaviors that involve higher risk compared to when they are well-fed. Here we explore the molecular details of this behavior in the invertebrate animal model C. elegans. This behavior, termed sensory integration, shows that C. elegans display reduced copper sensitivity when hungry. Copper is toxic and repellant to C. elegans; reduced avoidance indicates that these animals use riskier food search behaviors when they are hungry. Luckily, like us, this behavioral change is reversible upon re-feeding. This hunger-induced behavioral change is not due to increased attraction to food or depletion of fat stores, but rather insulin signaling between the intestine and specific neurons. We use genetic tools, microscopy, and behavioral tests to determine that this risky behavior involves sensation of "lack of food" in the intestine, release of signaling molecules, and engagement with sensory neurons. Our work highlights new and potentially evolutionarily conserved ways in which intestinal cells and neurons communicate leading to largescale behavioral change, providing further support for the importance of the gut-brain-axis.

neuroscience↗